3 - Pattern Recognition Receptors - Angyal

Question 1

What are PAMPs? and give 2 examples

Answer 1

Pathogen Associated Molecular Patterns

• differ from self cells
• critical to the survival/function of the pathogen therefore cannot differ too much and will most always be recognised by innate cels
• • shared by many microbes
• eg lipoteichoic acid - G+ve, LPS G-ve

Question 2

What are DAMPs?

Answer 2

Damage Associated Molecular Patterns

- host-derived molecules indicative of infection, stress, transformation, cellular damage

Question 3

What are the 4 receptors of the innate immune system and describe v briefly what they do?

Answer 3

cytoplasmic signalling receptors, membrane-bound phagocytic, membrane-bound signalling, soluble receptor
- job is to recognise conserved/relatively invariant patterns frequently found on pathogenic surfaces

Question 4

Give examples of PAMPs for bacteria, viruses, fungi and protozoa

Answer 4

Bacteria; G+ve lipoteichoic acid, G-ve LPS, flagellin (normally monomeric broken down version), unmethylated CpG DNA, N-formylated proteins (fMLP)
Viruses; dsRNA
Protozoa; mannose rich glycans, GPI-linked proteins
Fungi; B-glycan, chitin

Question 5

Give some examples of DAMPs

Answer 5

• mitochondrial components (should be in mitochondria)
• DNA (should be in nucleus)
• phosphatidylserine. normally kept on intracellular side of membrane by flippases. when cell undergoes apoptosis flippases stop working, PS can then be released -> extracellular side
• HMGB1 (high mobility group box 1 proteins), histones that should be bound to DNA but found in cytoplasm
• uric acid - indicative of kidney damage, oxidative stress
• heat shock proteins - eg Hsp70 responds under stress

Question 6

Are PRRs expressed exclusively by cells of innate immune system?

Answer 6

NO PRRs expressed by both immune and non immune cells (encoded for by germline)

Question 7

Give the 4 types of PRR and give examples of each

Answer 7

• soluble receptors (complement, ficolins, MBL)
• membrane bound phagocytic (complement, mannose receptors, scavenger)
• membrane bound signalling (scavenger, TLR4)
• cytoplasmic signalling (NOD-like, TLR7/8)

Question 8

What do soluble receptors recognise?

Answer 8

DAMPs - altered self/non self molecular patterns

Question 9

What is efferocytosis and why is it important that it is done?

Answer 9

soluble receptors are important opsonins that aid the clearance of apoptic cells. prevents inflammation being induced in tissue when not needed

Question 10

What are NETs and name 2 soluble receptors that recognise these?

Answer 10

NETs - released genomial, mitochondrial DNA

recognised by collectins , ficolins

Question 11

What is the long name for collectins?

Answer 11

collagenous lectin-binding proteins

Question 12

What is the structure of a collectin?

Answer 12

collagen domain and a Ca2+ binding domain

Question 13

Describe the 2 types of collectin proteins from the lecture

Answer 13

SP-A. expressed by lung alveolar macrophages that can bind to and aid clearance of pathogens
SP-D binds to genomic DNA/phospholipids and Abs and can also aid in the clearance of pathogens

Question 14

Describe the 3 types of membrane - bound phagocytic receptors and

Answer 14

• scavenger receptors. recognise anionic polymers, acetylated LDL eg CD14 recognises LPS, CD36 -> LDL
• complement receptors
• C-type lectins eg macrophage mannose receptors

Question 15

What type of receptor (of the 4 described) are chemotactic receptors on phagocytes?

Answer 15

membrane-bound signalling

Question 16

How do chemotactic receptors on phagocytes allow phagocytes to stop infection? Give an example

Answer 16

chemotactic receptors bind CHEMOATTRACTANTS and allow them to move to the site of infection, they also increase efficency of intracellular killing. eg neutrophils have fMLP receptors which bind to Nformylated proteins (common on bacteria) and therefore migrate to the site of infection because higher conc of fMLP here

Question 17

Describe TLRs ie how many in humans? where they’re located? how it differs from drosophila toll? names of different Toll.

Answer 17

Toll-Like receptors. membrane-bound signalling. 10 in humans/12 in mice that each recognise distinct PAMPs. located on cell surface and on intracellular membranes eg endoscopes. differ to drosophila toll because bind directly to microbial ligands (drosophila interact w/ pathogen products vi other proteins). TLR1/2/4/5 on SURFACE and TLR3/7/8/9 ON ENDOSOMAL membrane

Question 18

Draw the 2 structures of a TLR (one of the individual structures and a 2nd of how they all join up)

Answer 18

311 - 3

Question 19

Name 2 TLRs, what are their ligands and what cells are they found in?

Answer 19

TLR3 - dsRNA (viruses) found in macrophages, dendritic cells, intestinal epithelium
TLR4 (and MD-2/CD14) - LPS (G-ve), Lipoteichoic acid (G+ve).
Found on macrophages, dendritic cells, mast cells, eosinophils

Question 20

Describe the complex that recognises LPS

Answer 20

TLR4 monomer with MD-2 adaptor protein required to reach cell surface membrane. CD14 (membrane bound or free) concentrates (extracellular) LPS and allows it to bind to TLR4. promotes dimerisation. (shown in 311-3 word)

Question 21

Draw a diagram and explain the TLR mediated signalling pathway.

Answer 21

see 311 - 3 word doc

Question 22

Name the 2 types of cytoplasmic receptors.

Answer 22

NOD-like receptors (NLRs) and RIG-1 like receptors

both PRRs

Question 23

What does NOD stand for?

Answer 23

nucleotide binding oligomerisation domain

Question 24

What are NLRs and what is the result of their activation?

Answer 24

cytoplasmic sensor receptors that recognise bacterial components eg peptidoglycan, flagellin. signal expression of pro-inflammatory cytokines and (for eg NLRs in neutrophils) signal expression of enzymes to produce NO.
can also trigger assembly of inflammasomes.

Question 25

What are the functions of NOD1/2?

Answer 25

have caspase recruitment domain (CARD)

recruit components of cascade cascade -> apoptosis

Question 26

What are inflammasomes?

Answer 26

cleave and activate procytokines to cytokines so they can become active and released from cell

Question 27

What does RIG-1 like receptor stand for?

Answer 27

retinoic acid inducible gene

Question 28

What do RIG-1 like receptors recognise and what do they result in following activation?

Answer 28

Recognise viral ssRNA uncapped that is produced w/in the cell. signal expression of interferons (because these are v helpful in viral responses)